| Pan-CC chemokine neutralization restricts splenocyte egress and reduces inflammation in a model of arthritis. | |
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MedLine Citation:
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PMID: 20644170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chemokines are key regulators of leukocyte trafficking and play a crucial role under homeostatic and inflammatory conditions. Because chemokines are involved in multiple pathologies, they represent an attractive class of therapeutic targets. However, because of the redundancy of this system, neutralizing a single chemokine may be insufficient to achieve therapeutic benefit. Our strategy was to use a Fc-fusion recombinant protein form of the poxvirus-derived viral CC chemokine inhibitor protein (vCCI-Fc) that has the ability to specifically bind to multiple CC chemokines and neutralize their activity. In this study, we demonstrate first that, in vivo, vCCI-Fc prevents CC chemokine-dependent migration of macrophages into inflamed tissue of carageenan-challenged mice. We next studied this effect of inhibiting CC chemokine activity in a model more relevant to human disease, collagen-induced arthritis. Mice receiving vCCI-Fc revealed a striking retention of splenocytes, including activated and IFN-gamma-secreting CD4(+) and CD8(+) T cells, that was associated with a concomitant decrease of cells in the draining lymph nodes. These phenomena resulted in a significant decrease in the incidence of disease and a reduction in clinical score, joint inflammation, and cartilage destruction as compared with mice receiving isotype control. Taken together, these results define a role for CC chemokines in the control of disease, as interfering with their function leads to a previously unappreciated role of controlling inflammatory cell trafficking in and out of secondary lymphoid organs. |
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Authors:
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Vanessa Buatois; Séverine Fagète; Giovanni Magistrelli; Laurence Chatel; Nicolas Fischer; Marie H Kosco-Vilbois; Walter G Ferlin |
Publication Detail:
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Type: Journal Article Date: 2010-07-19 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2544-54 Citation Subset: AIM; IM |
Affiliation:
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NovImmune SA, Geneva, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arthritis, Experimental / immunology*, prevention & control Cell Line, Tumor Cell Movement / drug effects, immunology Chemokines, CC / antagonists & inhibitors, immunology*, metabolism Female Flow Cytometry Humans Immunoglobulin Fc Fragments / genetics, metabolism Inflammation / immunology*, prevention & control Interferon-gamma / immunology, metabolism Lymphocyte Count Macrophages / cytology, immunology, metabolism Male Mice Mice, Inbred C57BL Mice, Inbred DBA Protein Binding Recombinant Fusion Proteins / immunology*, metabolism, pharmacology Spleen / cytology, immunology, metabolism T-Lymphocytes / drug effects, immunology, metabolism Vaccinia virus / genetics, metabolism Viral Proteins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chemokines, CC; 0/Immunoglobulin Fc Fragments; 0/Recombinant Fusion Proteins; 0/Viral Proteins; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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